Guzek J P, Cline D J, Row P K, Wessels I F, Beeve S, Ispirescu S, Aprecio R M, Kettering J D, Gano D L, Nelson G M
Margaret Marquart Catholic Hospital, Kpando, Ghana, West Africa.
Invest Ophthalmol Vis Sci. 1998 Oct;39(11):2012-7.
To develop a model for experimental Streptococcus pneumoniae keratitis and to evaluate the chemotherapeutic efficacy of 12 common topical antibiotics in vivo.
Five-hundred (CFUs of log-phase S. pneumoniae were injected into the central corneal stroma of 36 eyes of 18 rabbits. After 0, 4, 8, 16, 24, and 48 hours, the in vivo growth was assayed as the CFU per cornea. Epithelial removal (to promote antibiotic entry and mimic human keratitis) was evaluated. Disc or tube dilution verification of the sensitivity or resistance of three S. pneumoniae strains was performed: a penicillin sensitive ("S"), an intermediate sensitive ("I"), and a resistant ("R") strain. Keratitis was established with S. pneumoniae "S" in 65 eyes, S. pneumoniae "I" in 107 eyes, and S. pneumoniae "R" in 78 eyes. Sixteen hours later, control corneas were harvested and the epithelium removed from treatment corneas. Every half hour saline, penicillin, gentamicin, bacitracin, ciprofloxacin, ofloxacin, erythromycin, vancomycin, ceftriaxone, cefotaxime, or chloramphenicol was applied for 5 hours. One hour later CFUs/cornea were assayed.
After 24 hours, S. pneumoniae "S" and "I" had proliferated to 9.18+/-6.65 x 10(6) CFUs and 9.26+/-6.90 x 10(6) CFUs. Epithelial removal at 16 hours was not significant. The in vitro antibiotic sensitivity was as expected. However, in vivo, penicillin, gentamicin, or cefazolin sterilized S. pneumoniae "S." S. pneumoniae "R" responded best to fortified gentamicin with or without vancomycin; all others antibiotics were significantly less effective (P < 0.001).
A small intracorneal S. pneumoniae inoculum in rabbit corneas grew and was maintained for 24 hours (with epithelial removal) to provide a model for testing antibiotic sensitivity in vivo. Topical penicillin is best for treating keratitis from penicillin-sensitive S. pneumoniae, whereas topical gentamicin or a combination of gentamicin and vancomycin was most effective against penicillin-resistant S. pneumoniae.
建立实验性肺炎链球菌角膜炎模型，并评估12种常见局部用抗生素的体内化疗效果。
将处于对数生长期的肺炎链球菌500个菌落形成单位（CFUs）注射到18只兔子36只眼的角膜中央基质中。在0、4、8、16、24和48小时后，测定每只角膜的CFUs以评估体内生长情况。评估上皮剥脱（以促进抗生素进入并模拟人类角膜炎）情况。对3株肺炎链球菌进行纸片或试管稀释法药敏或耐药验证：一株青霉素敏感（“S”）、一株中介敏感（“I”）和一株耐药（“R”）菌株。用肺炎链球菌“S”株感染65只眼、肺炎链球菌“I”株感染107只眼、肺炎链球菌“R”株感染78只眼建立角膜炎模型。16小时后，收取对照角膜并去除处理角膜的上皮。每半小时应用生理盐水、青霉素、庆大霉素、杆菌肽、环丙沙星、氧氟沙星、红霉素、万古霉素、头孢曲松、头孢噻肟或氯霉素，持续5小时。1小时后测定每只角膜的CFUs。
24小时后，肺炎链球菌“S”株和“I”株分别增殖至9.18±6.65×10⁶CFUs和9.26±6.90×10⁶CFUs。16小时时的上皮剥脱无显著差异。体外抗生素敏感性符合预期。然而，在体内，青霉素、庆大霉素或头孢唑林可杀灭肺炎链球菌“S”株。肺炎链球菌“R”株对强化庆大霉素（加或不加万古霉素）反应最佳；所有其他抗生素效果明显较差（P<0.001）。
在兔角膜内接种少量肺炎链球菌可生长并维持24小时（上皮剥脱时），以提供体内抗生素敏感性测试模型。局部应用青霉素最适合治疗青霉素敏感的肺炎链球菌性角膜炎，而局部应用庆大霉素或庆大霉素与万古霉素联合应用对青霉素耐药的肺炎链球菌最有效。
